In this article:
- What is cytogenetics?
- Making it work with the IT department
- Reliable results mean success
Opened: October 3, 2011
Staff size: 11 people on staff, including a technical coordinator, resource coordinator, six cytogenetic technologists, one technician, medical director, and manager.
Main focus: Conventional cancer cytogenetic and FISH analysis for leukemia and lymphoma, paraffin embedded tissue (PET) FISH analysis in breast cancer, brain tumor and lung cancer
System size: Northwestern Memorial Hospital is an 854-bed facility with more than 50,000 admissions per year
Test volume: About 6,000 tests per year for cytogenetics and FISH analysis
Patient community: Newborns to elderly, all specialties
Current test menu: Conventional chromosome analysis, FISH analysis of leukemia, PET tissue FISH
Interview with Yanming Zhang, M.D., Associate Professor of Pathology, Department of Pathology, Northwestern University; Medical Director, Cytogenetics Laboratory, Northwestern Memorial Hospital.
Were you involved in the development of the Cytogenetics Laboratory at Northwestern Memorial Hospital? How did that opportunity arise?
“I started at Northwestern University in 2011, and built the new cytogenetics lab from scratch. Northwestern University had been looking for a medical director with expertise to open a new cytogenetics lab — primarily for leukemia — for many years before I was identified. There was a big concern that they were sending out a lot of samples. The reference labs were far away from the hospital, and results took longer than what they wanted. The correlation of cytogenetic and FISH results with pathologic results was not prompt. It was also not perfect for residents and fellows in training due to lack of a cytogenetics lab in house. I was the assistant director, and then the associate director, of the cancer cytogenetics lab at the University of Chicago Department of Medicine, Section of Hematology/Oncology. I worked with Dr. Michelle Le Beau, Director of the lab and Director of the Comprehensive Cancer Research Center at the University of Chicago. I had six years of extensive experience running a clinical cytogenetics laboratory — cancer cytogenetics in particular — and I have obtained solid skills in reviewing, interpreting and reporting cytogenetic results. I also have good communication skills with physicians and pathologists. So the Northwestern opportunity was a perfect match for me.”
What is cytogenetics?
“Cytogenetics is a technology that looks at the chromosomes of human cells. We utilize cytogenetic and FISH techniques to look for chromosome and gene abnormalities in cancer, particularly leukemia and lymphoma. It is evident that cancer is a genetic disease. Although people will have different types of cancer, they usually share a similar genetic aberration and mechanisms with the same type of tumors. Thus, the detection of recurring chromosome abnormalities using cytogenetic techniques can help make precise diagnosis, decide the best treatment protocols and, most important, predict disease prognosis.”
Did you have to present your plans of a molecular lab to an administrative board to move forward?
“Before I joined in 2011, Northwestern University and Northwestern Memorial Hospital understood that this lab was desperately needed for better patient care and clinical service; they had a generous budget already. I provided my plan of what kind and how many test menus we would do, and what instruments and space I would need for each bench area. I also had some information on the current send-out cases and test numbers. I designed the lab including renovation, equipment, tests, the protocol training and quality control measures. I talked with the hospital administrators and my department chairman at various times about my plan. I am glad they gave me their full support. I always kept them updated on the progress of establishing the lab.”
Did you encounter any challenges in the development or building process?
“Information technology (IT) support from the hospital was a challenge. I believe this is a common challenge for many clinical labs. Because the laboratory needs a database for reporting, and a back-up system for all cytogenetic and FISH images, IT support was critical to make the lab work. I worked hard to get this done. I spoke with the department chairman and the hospital administrators; they helped me a lot and made IT support available. Now we have computer imaging that is on the IT server. All metaphase images are backed up every night on the IT server. The database system is also supported by the IT server. It’s not always quick, but we get support. We are working to get the microarray system backed-up as well. What I learned is that communication is critical. Once the IT group and the hospital administrators know that this is a priority, it often gets worked out.”
Whom did you turn to for advice when building your molecular lab?
“I was quite fortunate that I have several people to consult with. My mentors at the University of Chicago, Drs. Janet D. Rowley and Michelle M. Le Beau gave me many suggestions and ideas on how to keep the lab operating efficiently and at a high standard. They helped me learn how to work with hematopathologists and the molecular lab to get the maximum benefits for patient care. Dr. Rowley advises that physicians, pathologists and cytogeneticists work together closely to identify new correlation between genetics, morphology and disease treatment. When I was on the Central Cytogenetics Reviewing committee of the Cancer and Leukemia Group B (CALGB), I consulted with senior members, such as Dr. Betsy Hirsch from the University of Minnesota, who gave me various suggestions on establishing a new academic cytogenetics lab. I am also lucky that Dr. LoAnn Peterson, head of the hematopathology at Northwestern University, and her team understand the significance of the cytogenetics lab and gave me extremely strong support. For someone who may not have those connections, be proactive and approach those with a lot of experience. I find they will welcome you and are willing to share their experiences.”
How did you determine your test menu?
“At this time, the cytogenetics lab is specialized in cancer and I knew what tests were available. The hospital has a very strong leukemia, lymphoma, and myeloma programs, and a stem cell transplant clinic; so I knew what was needed. In addition, there are many PET FISH requests to study for certain gene amplification or deletions for breast cancer and brain tumors. I worked with physicians and pathologists to make sure what I planned to do were what they needed. I wanted to establish a test that is clinically beneficial to patient care, such as providing treatment choice, and is critical for making a precise diagnosis according to the WHO classification. You don’t want to bring in a test that is run only five times or so a year. The test menu has to be based on patient need, and in general it will bring revenue for the hospital.”
What kind of space did you have to work with when developing your molecular lab? “Based on standard cytogenetics procedures, I requested four independent, but connected rooms for culturing, harvesting, dropping and banding, case analysis, and for FISH process and analysis including a dark room for fluorescence microscopes. We have about 2,500 square feet. I created the plan and the hospital hired a company with a project manager to deal with materials and labor. Each technologist has a cubicle in the analysis room so they can do chromosome analysis and prepare draft reports, etc. So far it is enough space, but we plan to expand to cover prenatal cytogenetics. We also need some additional space to perform pre-PCR preparation for microarray studies in cancer.”
What should lab directors take into consideration when looking at new tests and automation?
“Before bringing in a new test or new technology, first make sure that the test and its significance is well confirmed and duplicated in a large series of studies. It is your responsibility to search for publication and contact the experts to confirm that the test is beneficial for patient care. Also, check with physicians to see how many cases will be ordered annually for this new test. That way you can determine how many full-time employees are needed to finish the tests, and the costs for reagents and equipment. Make sure the test is well-established through a systematic validation plan, and the technologists are well-trained. Training is very important, as well as quality control and trouble shooting skills. As director, you must be involved directly when establishing the new tests — including bench work — so you know how to troubleshoot.”
“In terms of automation, make sure it is good quality; look at the benefits, and be aware of quality control. There are several machines for cytogenetics and FISH analysis, such as for automatic harvesting, metaphase scanning and FISH signal scoring. We have an automatic chromosome scanner. It helps us a lot because the machine can run overnight, and the next morning the tech can look at images immediately. If I am going to bring in an automated machine, I want to look at how much the machine will help me to reduce technologists’ time, and if the quality is at the same level with manual processing. An extensive validation is essential prior to implementing a new machine in order to keep high quality in cytogenetic and/or FISH analysis.”
How do you measure the success of your lab?
“For our lab, I want to see reliable results. It is important to read them accurately. Every three months, I check how many cases were abnormal, normal and how many were inadequate. I check to see how well our results correlated with morphology, flow and molecular results. If we have a precise, high-quality analysis and reliable results, and our service meets the requirements of physicians for patient care — that is success. In addition, good communication with the clinic and lab is also very important to share useful information for better patient care. I am glad that our physicians have confidence in our service.”